Active site electronic structure

The very large amount of data currently available on the Cu2Zn2 SOD enz5mie has enabled a deep understanding of its function and to the rationalization of most aspects of its chemistry and biochemistry. Different techniques have allowed the enzyme to be probed in all its aspects, from the finest details of the active site electronic structure to the overall description of its molecular assembly. The theoretical work has further completed and linked most aspects of this information. However, some parts of the picture are still fuzzy. There are aspects that in our opinion need further study ... 

These enzymes continue to be the subject of intense research efforts, and this is a direct result of their unusual geometric and electronic structures, their key roles in the global C, N and S cycles, their pharmacological importance, and their importance in human health. This volume will detail how spectroscopy, structure, electrochemistry and theory have been used to develop a comprehensive description of the active site electronic structure contributions to reactivity in pyranopterin Mo enzymes and the Mo-dependent nitrogenase. A particular emphasis is placed on how these important studies have been used to reveal critical components of enzyme mechanisms. 

The initial contribution to this volume provides a detailed overview of how spectroscopy and computations have been used in concert to probe the canonical members of each pyranopterin Mo enzyme family, as well as the pyranopterin dithiolene ligand itself. The discussion focuses on how a combination of enzyme geometric structure, spectroscopy and biochemical data have been used to arrive at an understanding of electronic structure contributions to reactivity in all of the major pyranopterin Mo enzyme families. A unique aspect of this discussion is that spectroscopic studies on relevant small molecule model compounds have been melded with analogous studies on the enzyme systems to arrive at a sophisticated description of active site electronic structure. As the field moves forward, it will become increasingly important to understand the structure, function and reaction mechanisms for the numerous non-canonical [ie. beyond sulfite oxidase, xanthine oxidase, DMSO reductase) pyranopterin Mo enzymes. 

Active Site Electronic Structure Contributions to Reactivity... 

This review addresses these issues from the perspective of the electronic structures of the [FeX4] (X = Cl , SR ) redox couples and their influence on ET parameters. These sites are probed using a combination of spectroscopic methods and theoretical results from density functional (DFT) calculations. The available experimental data for the ferric complexes are presented in Section 2.59.2, providing a detailed description of the active site electronic structure when combined with results from DFT calculations. In Section 2.59.3, a similar analysis is performed on the ferrous complexes with focus on the differences and similarities between the reduced and oxidized sites and between the chloride and thiolate redox couples. Section 2.59.4 provides a mechanism to quantitatively evaluate the changes in the electronic structure of a site on redox, this is electronic relaxation. The information presented in Sections 2.59.2-2.59.4 is used in Section 2.59.5 to evaluate the influence of electronic structure on A //da> and E. ... 

Lowery MD, Guckert JA, Gebhard MS, Solomon El. Active-site electronic structure contributions to electron-transfer pathways in rubredoxin and plastocyanin direct versus superexchange. J Am Chem Soc 2002 115 3012-3013. 

Dinitrogenase has been crystallized and its tertiary structure determined by Kim and Rees. [44, 45,46] As indicated, an Fe-Mo unit serves at the active site. Electrons are furnished to this active unit by the Fe enzyme dinitrogenase reductase. The two units together constitute nitrogenase. 

Animal FASs are functional dimers [76]. While /3-ketoacyl synthase requires dimer formation for activity [77], catalysis of the remaining FAS reactions is carried out by the monomeric enzyme. This behavior is reminiscent of yeast fatty acid synthase, where the -ketoacyl synthase and ACP from different subunits also contribute to the same active site. Electron microscopy and small angle scattering experiments have further defined the structure of the functional complex [34,78]. The overall shape of the molecule, as visualized by electron microscopy, is two side by side cylinders with dimensions of 160x146 x 73 A [34]. 

Electrons from cytochrome c are donated to the dinuclear copper centre Cua, and then transferred consecutively one at a time to haem a, and from there to the dinuclear haem-copper (haem u -Cua) catalytic centre. A tyrosine residue, Y(I-288), which is covalently cross-linked to one of the Cub ligands (His 240), is also part of the active site. The structure of the four-subunit CcO from R. spheroides is presented in Figure 13.9(a), while a more detailed view of the redox-active cofactors and amino acid residues involved in the proton transfer pathways is given in Figure 13.9(b) (Brzezinski Johansson, 2010). 

A catalyst is a material that accelerates a reaction rate towards thennodynamic equilibrium conversion without itself being consumed in the reaction. Reactions occur on catalysts at particular sites, called active sites , which may have different electronic and geometric structures than neighbouring sites. Catalytic reactions are at the heart of many chemical industries, and account for a large fraction of worldwide chemical production. Research into fiindamental aspects of catalytic reactions has a strong economic motivating factor a better understanding of the catalytic process... 

From a map at low resolution (5 A or higher) one can obtain the shape of the molecule and sometimes identify a-helical regions as rods of electron density. At medium resolution (around 3 A) it is usually possible to trace the path of the polypeptide chain and to fit a known amino acid sequence into the map. At this resolution it should be possible to distinguish the density of an alanine side chain from that of a leucine, whereas at 4 A resolution there is little side chain detail. Gross features of functionally important aspects of a structure usually can be deduced at 3 A resolution, including the identification of active-site residues. At 2 A resolution details are sufficiently well resolved in the map to decide between a leucine and an isoleucine side chain, and at 1 A resolution one sees atoms as discrete balls of density. However, the structures of only a few small proteins have been determined to such high resolution. 

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